ImprovingtheHumanCondition

DavidZhu,CarmenNg,CamilleMcAvoy,PedroFigueroa

Itwouldmakethe“choosetwo:{sleep,grades,friends}”dilemmasomuchsimpler…

Importance Sleepaffectseveryone! Seriousproblems/effectsofsleepdeprivation

Decreasedmentalfunction(memory,recognition,etc.) Cardiovascularproblems,weightgain

Impact Startwithspecificapplications:large“delta”forsmallpopulation Military,Collegestudents,etc.

Expandtobroadapplications:smaller“delta”forlargepopulation Generalproductivitybooster?

Short‐andlong‐termhealthrisks?

Knowns/Unknowns Muchisstillunknownaboutsleep

Whydowesleepatall? Whataretheresultsofsleeping?

Whatweknowaboutsleep 4Stages:N1,N2,N3,REM Occursincycleslasting90‐110mins.

N3,REMare“deepsleep”cycles REMonlyaccountsfor~30%ofsleep

Possibleto“isolate”REMsleep?

Competition Manyresearchinstitutionsareinvestigatingthecauses/effectsofsleep

Drugstimulants Caffeine! Modafinil

OurIdea “Curing”sleepmightbetooambitious,givenhowlittleisknownaboutthecausesofsleep

Increasetheleveloftoleranceforcaffeinebymanipulatingtheadenosinereceptors

Althoughsleepisnotfullyunderstood,themanipulationofneuralreceptorscouldplayanimportantroleinincreasingtolerancetosleepdeprivation

Anotherimportantmethodforimprovingthefunctioningofthebrain,andparticularlyforhealingthedamagedbrain,isthroughtheregenerationofneurons

Braindamage?Noproblem!

Importance Thereisnowaytorepairdamagedneurons Seriousproblems!

Lossofmotorfunctions Braindisorders Deadneurons

Impact Affectsonlyalimitedsegmentofthepopulation(injury,Alzheimer’s,etc.)–butimpactwouldbetremendous.

Wouldallowthosewhosufferfrombraindamagetohavereturnedphysicalandmentalfunctioning

CompetingTechnologies Useofstemcellstoreplacedamagedneurons Stimulationofnervecellstohelpregrowneuralconnectionsinthebrain

Turningofforblockingpathwaysthatinhibitregrowthofneurons ThreeinhibitorsofaxonregrowthknowntodateareNogo,myelin‐associatedglycoprotein(MAG)andmyelin‐oligodendrocyteglycoprotein(OMgp)

Knowns Basicstructureofneurons Neuralpathwaysandtheuseofneurotransmitterstocommunicatewithinthebrain

Neuronscanberegeneratedwiththeuseofstemcells

Unknowns Efficienttechniquesforreplacingdamagedneurons

Natureofgenesassociatedwiththeregenerationofneurons

•Neuronswithintheadultbrainthatregrowaxialprojectionshavebeenfound,butthegenesthatencodeforthisgrowthandtheproteinsthattheytranslatearenotwellknown

Insertingregeneratedneuronsintothebrainorstimulatingtheregenerationofneuronswithinthebraincouldallowfortherecoveryofmentalandphysicalfunctioning

•Neuronregenerationcouldhelptocurepatientswhosufferfromneurodegenerativediseases,suchasAlzheimer’s

Importance

Highlydegenerativediseasethatisultimatelyfatal Lowersthequalityoflifeanddecreasesthecapacitytofunctionofsocietyofthosewhosufferfromit

Anestimated26.6millionpeople65yearsandolderhadAlzheimer’sworldwidein2006

ThusAlzheimer’shasterribleandirreversibledegenerativeeffectsonalargenumberofpeople

Impact Memorymakesyouwhoyouare! WillhelppeoplewithAlzheimer’sandotherformsofdementiaretaintheirlifelongexperiences

Preservesfamilyunity ReducesHumanSuffering

Howtostoptheloss? Rearrangethefiberstotheiroriginalposition KILLtheplaques Weareproposingtomonitorthemusing“bio‐markers”

Blood‐BrainBarrier LimitedImagingoftheBrain

IssuesforTreatment

Knowns SenileplaquesandneurofibrillarytanglesaredirectlyassociatedwithAlzheimer’s

PossibleGeneticComponent:MutationsonChromosomes9and19

Thecellsultimatelydie Causesthebraintoshrink Proteinpiecesclumptogetherinthebrain Chemically“sticky”(theybondeasily) Theclumpsblocksignalsandultimatelykillthecells!!

Unknowns Whatcausesplaquestoform Whattypesofneuronsareaffected

Whyarecertainareasofthebrainaffected

Structureoftheproteinplaques Timethatittakestheclumpstobe“big”enoughtoblocktheneuro‐signals

“Twisted”Proteins:Whatcausesthemtoentangle?

CompetingTechnologies ManypharmaceuticaltreatmentsfocusonneurotransmittersNOTonplaquesandtangles

ClinicalTrials TheU.S.FoodandDrugAdministrationhasapprovedfourdrugstotreatAD.ForpeoplewithmildormoderateAD,donepezil(Aricept®),rivastigmine(Exelon®),orgalantamine(Razadyne®).

Namendaregulatesglutamatewhichplaysakeyroleinprocessinginformation.

TreatmentsResearched:Breakingdownbeta‐amyloidplaques,anti‐inflammatorydrugs

Summary Manipulatingreceptorsonneuronscanplayamajorroleinthetransferof

informationthroughneuralpathways Changingadenosinereceptorscanhelpincreasetolerancetocaffeine

Caffeinesupplementscouldbemorecontinuouslyeffectiveindecreasingtheneedforsleep

Changingneuralreceptorscanalsoallowforspecificdrugtreatmentsandchemicalstobetransferredtoneuronsformedicinalpurposes

Regenerationofneuronsisamajorconcernsincemostneuronsareinastateofnon‐replication

TheregenerationofneuronscouldallowforthetreatmentofpatientswithAlzheimer’sandotherformsofdementia

TheremovalofplaquesandthedetanglingofneurofiberscouldimproveneuralfunctioningandultimatelyhelptopreventtheprogressionofAlzheimer’s

Resources http://www.pnas.org/content/100/13/7430.full http://www.alseres.com/science‐technology/nerve‐repair.asp http://www.narcis.info/research/RecordID/OND1325851/Language/en/;jsessio

nid=i0hc281m2bl http://alzheimersdiseaseaid.com/origins‐unknown‐‐the‐battle‐with‐

alzheimer‐s‐continues.php http://www.nia.nih.gov/Alzheimers/AlzheimersInformation/Treatment/http:/

/alzheimers.about.com/od/treatmentofalzheimers/a/treatments.htm http://web.mit.edu/newsoffice/2008/alzheimers‐protein‐

0821.htmlhttp://www.nanowerk.com/spotlight/spotid=5262.php